Revista de Gastroenterología del Perú - Volumen 19, Nº1 - 1999

TEMAS DE REVISIÓN

Mini-Endoscopy of the Biliopancreatic System 1998

*Michael Jung

RESUMEN:

La pancreatoscopía es un método que aún está en los inicios de su desarrollo. Los instrumentos disponibles en la actualidad sólo permiten la inspección de partes del sistema ductal que dilatadas proximalmente.

Gracias a la pancreatoscopía, la endoscopía gastrointestinal se ha extendido a explorar el sistema glandular que posee una pared con una estructura histológica única. Los diversos procesos patológicos pancreáticos hacen deseable la existencia de métodos diagnósticos invasivos útiles. Sin embargo, esta técnica debe ser utilizada con especial cuidado por sus posibles complicaciones como la pancreatitis aguda.

La endoscopía del conducto biliar y del pancreático son técnicamente posibles y proveen la evidencia detallada que se requiere para el diagnóstico de las enfermedades del sistema pancreático y biliar. Las indicaciones de la colangioscopía están ya bien establecidas, fundamentalmente como acceso terapéutico a los cálculos difíciles. Los primeros prototipos para endosonografía pancreática ya están disponibles, sin embargo por ahora no se espera que esta técnica sea un procedimiento de rutina en el futuro cercano.

PALABRAS CLAVES: Pancreatoscopía, colangioscopía, sonografía intraductal, técnica, indicaciones.

 

Summary

Pancreaticoscopy is a method that is still in the midst of its development. The instruments available to date only allow inspection of proximally dilatated and extended ductal sections.

Thanks to pancreaticoscopy, gastroenterological endoscopy has left the intestinal tract and achieved access to a glandular system with a unique histological wall structure. The extensive pathological anatomy of the pancreas makes intensive diagnostics desirable. Pancreaticoscopy should therefore be included in the diagnostic spectrum. However, this technique should always be performed with special circumspection, in particular with regard to the possible complications (acute pancreatitis)

Ductal endoscopy of the bile duct and pancreatic duct are technically feasible and provide detailed evidence required for the diagnosis of diseases of the biliary and pancreatic system.

The indications for cholangioscopy have, for the most part, been established, specifically therapeutic access to difficult gall stones. Pancreaticoscopy opens up new terrain in medical optics, although the relevance of this method, in conjunction with the outlay and technique required for its use, still have to find justification. The first prototypes for endoluminal sound have become available although this method is not expected to become a routine procedure in the near future.

KEY WORDS: Pancreaticoscopy, cholangioscopy, intraductal sonography, indications, technique.

 

INTRODUCTION:

In biliopancreatic diseases, the traditional imaging procedures (abdominal ultrasound, CT, ERCP, EUS) only provide an indirect picture of the lesion. Imaging of strictures and stenoses in the biliary tract as in the pancreatic duct system is descriptive and subject to interpretation. Often, it is not possible to differentiate them into " benign" or "malignant".

Focal parenchymatous processes can be diagnosed microscopically by sonography-guided puncture, whereas intraductal sessile structures are lost to differential diagnostics.

A direct way to elucidate ductal stenoses and intraductal changes of the ducts is by means of papillary access. Following total sphincterotomy of the sphincter of the common bile duct, it is possible to perform endoscopy of the efferent biliary tract extending to where the hepatic hilum branches off, and sometimes even beyond this (Fig. 1 a + b). Similarly, when the ductal system is dilatated, Wirsungs duct can also be inspected in this way. Ductal endoscopy is performed with instruments of between 2.0 and 4.5 mm in diameter. In general, cholangioscopy is also possible via a percutaneous transhepatic access (via PTC) or a T-drain canal (1) .

Mini-endoscopy is performed using the mother-baby technique. Two experienced endoscopists who have worked together as a team each guide one instrument. The optical image is transmitted to two synchronized monitors. Mother-baby endoscopy is more complicated than the diagnostic or therapeutic ERCP. Manual dexterity in addition to routine with maneuvering around narrow ductal systems is needed.

 

Cholangioscopy

Instruments

Peroral cholangioscopy is usually performed with a wide- lumen side view instrument (mother endoscope) and a baby endoscope. The narrrower instrument is guided through the up to 5.0 mm wide instrumentation canal of the delivery endoscope. Babyscopes with diameters of between 3.1 and 4.5 mm are equipped with an instrumentation canal that can be used for rinsing, air insufflation, biopsy and lithotripsy. The smaller the baby endoscope, the more sensitive is its maneuverable distal end and its covering.

Currently, two companies commercially produce mother-baby systems that meet the requirements pertaining to external guidance of the distal end, rinsing and air insufflation of the ductal system. The sufficiently wide instrumentation canal also allows biopsies to be taken and intraductal therapies to be administered. Babyscopes of less than 2.5 mm have previously only been available as prototypes. They lack either a distal angulation or an instrumentation canal ( of up to 1 mm diameter). There is also the option of ductal passage via fine guide wires (1,2,3,4, Tab. 1).

Technique

For mother-baby endoscopy, the patient must be comfortably sedated. We recommend either midazolam or diazepam in combination with an analgesic (e.g. Fortral ®). Ideally, propofol (Disoprivan ®) is administered as a continuous infusion. Digital pulsoximetry and pernasal oxygen supply are desirable adjuncts. More time-consuming interventions on the biliary duct system (up to 1 h) should ideally be performed with the assistance of an anesthesiologist. The relaxation of the duodenum is achieved with intravenous Buscopan ® or Glucagon ®. The examination is very staff intensive. In addition to two endoscopists, two assisting nurses are needed (1 nurse for direct instrumentation and 1 runner), a monitoring physician (assistant/anesthesiologist) and, optionally, an x-ray specialist (assistant/radiology) must be present (Tab.2)

After placement of the Mother-endoscope in front of the split papilla, via a slight angulation of the distal end and gentle upwards movement of the Albarran elevator, the babyscope is guided towards the proximal, in the direction of the papillary stoma. Both endoscopists should perform these manipulations and the utmost of caution is advised here, since shearing around the Albarran elevator can cause destruction of the fiberglass system and allow water to enter into the distal end. The guide track over a guide wire designed as an introducer aid has the opposite effect when the access to the papilla is steep. If the guide track is too rigid, the kink in the babyscope is too extreme and breaks the optical fibers. The cholangioscopy is performed under optical (monitor) and radiological guidance (x-ray machine). The more difficult role in this undertaking is borne by the endoscopist maneuvering the mother device.

Consequently, the experienced examiner works the wide-lumen side-view instrument and ensures permanent stabilization at the papillary level.

Diagnostic cholangioscopy is primarily used to differentiate between stones and stenosis and aids in the histological processing of the stenosis. Tissue samples can be removed through the baby instrument using a fine biopsy forceps with spine. A high material yield is achieved by direct biopsy through the side-view instrument with a sufficiently large forceps. This strategy may therefore consist of a cholangioscopy without biopsy followed by sample excision using a larger forceps after removal of the babyscope.

Indications

Indications for cholangioscopy were drafted in 1992 at a German consensus conference. The main indications involve unclarified intraluminal structures and biliary stenoses for macroscopical and bioptical clarification (5)

Therapeutic endoscopy using the cholangioscope is primarily carried out for the treatment of large gallstones. Concrements that cannot be extracted or lithotripsied by classical methods (balloon, basket, mechanical lithotripsy), can be broken up intraductally. Lithotripsy within the bile duct is based on two different physical systems. The classical method uses electrohydraulic lithotripsy (EHL) the modern version of laser lithotripsy, e.g. with a Rhodamid 6 R laser (6,7,8,9).

The EHL method requires that the biliary tract is simultaneously rinsed via a parallel nasobiliary tube. In effect, the stones are broken up only in the liquid milieu. The lithotripsy tube must be in direct contact with the concrement. It is mandatory that contact with the stone is under optical control, as any slipping of the tube and spark discharges onto the ductal wall can lead to bleeding and perforation. Repeated impulses given with a foot pedal lead to continuous disintegration of the concrement. Spraying stone particles may briefly impair visibility and require continuos rinsing with fluids over the tube and babyscope. Extraction of the concrement particles is performed in the usual way (basket, balloon).

While it is important to maintain direct visibility during EHL destruction, laser lithotripsy is performed under purely radiological control. Modern laser systems (Lithognost ®, Baasel Laser Technique) whit 0.3 mm fine glass fibers are equipped with an automatic tone recognition system that relies on the spectroscopic analysis of the reflected light. Whenever the laser touches the wall of the duct, the laser shuts off automatically, thereby virtually eliminating wall injuries. Laser lithotripsy can be performed without babyscope, but is easier under direct optical control.

The laser stone recognition system is the most advanced type of intraductal stone therapy available to date (10) and its use has only been limited by the high investment costs and dissemination of the technique.

Results

Peroral cholangioscopy is technically possible in 90% of all desired examinations. It is dependent on the anatomy of the patient´s upper digestive tract (no gastric resection with Roux-Y anastomosis or Whipple’s operation) and on a sufficiently wide papillary access (sphincterotomy stoma). Optical differentiation between stone and stenosis appears easy, whereas distinguishing between a benign stenosis and a malignant stricture frequently causes problems. External tumor compression without infiltration of the ductal epithelium will seldom be bioptically evident. Malignant processes in the bile duct often exhibit a high portion of connective tissue that encumbers the biopsy (too hard, too little material) in addition to not providing a representative image of the stricture (11). Polypous and soft tumors – adenomas and carcinomas – are easy to identify macroscopically and to diagnose microscopically. A characteristic feature is the villous, often patchy growth pattern. Indirect evidence of malignancy may also be provided by dilatated and tortuous vessels within and around the stenotic segment (12). Moreover, pathological biliary mucosa can be distinguished from that of normal wall on the basis of granular or papillary pattern.

The bioptical yield of a cholangioscopy is frequently disappointing. Even with the help of cytology, classification of a stenosis into "malignant" or "benign" cannot be solved with satisfaction (13).

Therefore, ductal endoscopy in the biliary tract is chiefly used for stone therapy. EHL and laser lithotripsy have expanded the spectrum of endoscopic stone treatment very markedly. The reported success rate of intraductal stone therapy ranges between 70 and 100%. When access is unproblematic (wide papillotomy), complete eradication of the stones is generally the case.

The complication rate of diagnostic and therapeutic cholangioscopy is regarded as low (5). Serious infections or sepsis have not been previously described. But due to the still traumatic nature of the intervention, perioperative antibiotics with mezlocillin or amoxicillin is routinely give (14). Complications mostly involved are injuries to the bile duct. The Achiles‘heel of the method lies in the intrapapillary/retropapillary area. This is where perforations with the instrument are most likely. Bile duct injuries will also occur when the EHL tubes is applied improperly. The complications described thus far were mostly corrected by conservative interventions with a naso-biliary tube.

Summary

Peroral ductal endoscopy allows more comprehensive differentation of unclarified masses in the ductal system. Although macroscopical visualization leads to satisfactory results, microscopical diagnostics have not met up with expectations. It is entirely impossible to endoscopycally inspect the immediate prepapillary duct section.

By contrast, the method of intraluminal stone therapy has become established in the therapeutic sector. Laser lithotripsy shows a slightly higher efficiency and a lower complication rate. However, it is by far the more cost intensive procedure.

Mother-baby endoscopy is a technique reserved for experienced and skilled endoscopists. It requires a high outlay for staff and equipment and can only be recommended in centers where it is used frequently and the appropriate training takes place. Since imaging procedures are only descriptive, the indication for direct optical and bioptical verification is not eliminated.

Pancreaticoscopy

The endoscopic exploration of the pancreatic duct is more difficult than of the biliary system.

Anatomical anomalies and the narrow diameter of the duct restrict endoscopy of the ductal system from the onset. For endoscopes > 2 mm in diameter, it is necessary to cut the pancreatic sphincter. Nevertheless, for anatomical reasons, a stoma can never be made as large as in the bile duct papilla. The incision is made along the duct opening in the 2 o‘clock direction with complete separation of the papillary roof (15). A previous bile duct sphincterotomy is necessary in exceptional cases only.

The wall of Wirsung‘s duct is lined with a single layer of small cubic cells with a connective tissue covering. Muscular or elastic fibers like those in the biliary duct system are missing (16). When pressure in the papillary section increases (intubation, administration of contrast media), the pressure is transferred to all regions of the ductal system and into the parenchyma.

Unlike the situation in the biliary tract where the fibers are elastic, pressure reduction cannot take place. Postinterventional pancreatitis resulting from duct obstruction or retention of contrast media can develop. The primary aim is to maintain the flow of secretion which is guaranteed by a sphincterotomy that is wide enough and by postinterventional ductal drainage (nasopancreatic tube).

Technique

A number of prototype endoscopes have been designed for pancreaticoscopy (tab. 4). Finecalibration instruments of up to 0.5 mm in diameter reach the technical limits with surprisingly high imaging quality. But despite their good optical features, these instruments lack the distal maneuverability, a canal for rising and instrumentation and the necessary sturdiness of construction. The previously commercially produced pancreaticoscopes have diameters

in diameter. The canal can be used for rinsing and instrumentation, for excising biopsies and, if required, for hemostasis. If the duct shows the right diameter, a cholangioscope of 4.5 mm in diameter can be used. The 3.1 mm-devices (Pentax, Olympus) are also designed to be used as universal endoscopes for both bile and pancreatic ducts, although the endoscope is not always stable enough for the bile duct.

Pancreaticoscopy is performed according to the mother-baby technique. The starting angle for the babyscope is flatter than for access to the bile duct papilla. Thanks to the small outer diameter of the pancreaticoscope, a thinner side-view endoscope can be used, e.g. TJF 130 (Olympus) of 13.5 mm in diameter and with a 4.2-mm canal (Fig. 2 a, b, c).

Nevertheless, inspection of the pancreatic duct up into the tail region is rarely possible. Atraumatic duct exploration is only conceivable if the pancreatic duct is stretched virtually fully, a sphincterotomy has been done and the duct has a diameter of at least 6 mm. The use of a 3.1-mm babyscope always requires a sphincterotomy. Pancreaticoscopy with instruments of 0.5 to 2 mm in size can also be performed through the non-sphincterotomized papilla. Duct dilatation and straight duct course are prerequisite to pancreaticoscopy. More encompassing inspection is not possible with looping variants and angulations of Wirsung‘s duct. In such cases, the diagnostic examination must remain limited to the ductal system in the head region and virtually always stops at the knee from head to corpus (17, 18, 19, 20). The intravenous administration of secretin (1 mg/kg of body weight) stimulates the secretion in the pancreas and puts the ductal system "under water". Endoscopy in a liquid milieu can be advantageous because it avoids annoying air bubbles.

Biopsies are excised under visual control. Similar to the bile ducts, the small biopsy forceps produce a lower yield than the direct radiologically verified biopsy. Upon completion of the examination, drainage of the ductal system should be performed in all cases using nasopancreatic tubes with suitable diameters of 5-7 mm (e.g. nasopancreatic drainage set type NPDS-5,Cook Co., Mönchengladbach, Germany). Ductal drainage is also necessary when a total sphincterotomy is performed since any postinterventional papillary edema can quickly cause secrete blockage and herald pancreatitis. The tube is left in place for 24 to 48 hours and removed under radioscopic guidance using the guide wire. Optionally, antibiotics and octreotide analogs (sandostatin 100 ug every 8 hours) for reduction of secretion can be given postinterventionally.

Indications

In principal, every structure of Wirsung.s duct can be examined for malignancy. Any stenosis in the ERP image alone is not definite confirmation of the degree of malignancy.

Complementary examinations like endoscopic ultrasound (EUS) and CT do not always reproduce a clear image of the parenchyma in vicinity of the stenosis. Optical and bioptical elucidation of a stricture is therefore desirable, but encumbered by the specific anatomical and technical difficulties of this examination. Stenosis in the head of the pancreas, a little ways from the papilla is therefore the most likely to be reached and can occur in isolation or within the context of chronic pancreatitis.

Intraductal processes provide better access for the instrument when duct dilation is performed simultaneously. Pancreaticoscopy here aids the differential diagnosis of stone/tumor and has led to the diagnosis of papillary-mucinous tumors (20,21) (Fig. 3 a,b,c).

Elucidation of this type of tumor and its intraductal spread is currently regarded as the primary indication for pancreaticoscopy. The macroscopical appearance of these tumors is so impressive that diagnosis can even be rendered optically. The duct width and the gapping papilla stoma features accommodating pancreaticoscopy.

Results

Endoscopy of the pancreatic duct has not yet become a standardized procedure. Suitable instruments and broad empirical series are lacking that would document the relevance of this method (22). On the other hand, there are a number of unclear findings that can have therapeutic consequences. The previous reports suggest the importance of pancreaticoscopy, in particular, in intraductal processes and specifically in papillary-mucinous tumors.

Pancreaticoscopy can be a valuable method for diagnosing unclarified stenoses (17) (Fig.4 a,b,c; Fig. 5 a,b,c,d). Therapeutic pancreaticoscopy is basically possible. For example laser lithotripsy, or intraductal hemostasis can be performed under visual control, as required (23,24). However, the literature is limited to isolated reports of such interventions.

Intraductal Sonography

Intraductal ultrasound can be performed using side-view instruments that have a sufficiently wide (3.2 mm) canal. The previously available ultrasound tubes can be inserted into both the bile as well as the pancreatic ducts. Their size varies between 1.8 and 3.4 mm and their transducers vary between 7.5 and 30 MHz. Larger studies have used probes of 2.0 mm in diameter and 20 MHz frequency (Aloka Co., Japan). Although impressive 360º images of the bile duct are possible, the results achieved with this method to date have not been convincing (25). Tumor staging in the bile ducts and the interrelated differentiation between T1 and T2 tumors does not appear to be currently possible (26).

Endoluminal sound is also possible in the pancreatic duct. Its disadvantages are poor flexion of the tip of the tube so that only a short section of the pancreatic duct can be inspected. Endoluminal sound allows differentiation between stones and tumor formation. But this method has not become routine procedure, although its great potential for the future should not be overlooked (27).

a

b
Figura 1 a,b: Billiary endoscopy with regular left and right hepatic duct
a



Figura 2 a,b,c:
Difusse and irregular dilated pancreatic duct system in a patient with obstructive jaundice and tumor of the pancreatic head(CT-scan)
ERCP (Fig.2 a) Pancreaticoscopy with a 3,1 mm instrumentb (Fig.2 b,c)
Diagnosis: Papillary-mucinosis tumor of the pancreatic head

b

 

c

 

a pag54_fig3A.jpg (20859 bytes) b c
 
Fig. 3 a,b,c:
2-3 mm srtucture in the main pancreatic duct. ERCP(Fig.3a)Pancreaticoscopy with intraductal biopsy revealed an IPMT-Tumor (Histologie 3 b; PD Dr. G. Hermann, Scanckenbergisches Instituc der Pathologie Uniklinik Frankfurt am Main/Germany).
Circunferential tumor growth one year later (Fig.3c). Whipple's operation.
a b c
Fig.4 a,b,c: Stenosis of the pancreatic duct, mimicking pancreatic cancer. Pancreaticoscopy showed bening structure in sclerosing pancreatitis, allowing guide wire passage through the sticture. Non dilated irregular pancreatic duct in the tail with irregular side branches due to the inflammatory process. ERCP (Fig.4a+c) Endoscopy (Fig.4b)
Fig. 5 a,b,c,d. Pancreaticoscopy in 27 y old female patient (5a), demostrating pancreatic duct stone obstruction in the pancreatic head.(5b+c).
Stone removal and guide wire directed passage of a naso-pancreatic tube for descompresion of dilated duct (5d).

Literatur:

1.- Neuhaus, H.: Cholangioscopy. Endoscopy (1994)26: 120-125

2.- Barnett, J. L., Knol: Use of a novel, adoptable "baby cholangioscope to diagnose a bilary papillary adenoma. Gastrointest

3.- Sackmann, M.: Minicholangioscopy during routine endoscopic retrograde cholangioscopy. Endoscopy (1995) 41: 70-72

4.- Soda, K., K. Shitou, Y. Yoshida, T. Yamanaka, A. Kashii, M. Miyata: Peroral cholangioscopy using a new fine- caliber flexible scope for detailed examination without papillotomy. Gastrointest Endosc (1996) 43: 233-238

5.- Riemann, J. F., Mini- Endoskopie des bilio- pankreatischen Systems. Z Gastroenterol 31:156-157

6.- Hixson, L. J., M. B. Fennerty, P. E. Jaffee, J.H. Pulju. S.L. Palley: Peroral Cholangioscopy with Intracorporeal Electrohydraulic Lithotripsy for Choledocholithiasis. Am J Gastroenterol (1992) 87: 296-299)

7.- Hochberger, J., E. G.Hahn : Perkutane und transpapillare Cholangioskopie: neue diagnostische und therapeutische Moglichkeiten . Schweizer Rundschau Med (Praxis) 81 (1992) 917-920

8.- Binmoeller, K. F., M. Brückher, F. Thonke, N. Soehendra: treatment of difficult bile duct stones using mechanical ,electrohydraulic and extracorporeal shock wave lithotripsy. Endoscopy (1993)25: 201-206

9.- Ell, C., J Hochberger , A. May , W. E. Fleig , R. Bauer, L. Mendez., E.G. Hahn: Laser lithotripsy of difficult bile duct stones by means of a rhodamine- 6G Laser and an integrated automatic stone -tissue detesction system. Gastrointest Endosc. (1993) 39: 755-762

10.- Neuhaus , H ., W. Hofmann, K . Gottlieb, M. Classen: Endoscopy Lithotripsy of bile duct stones using a new laser with automatic stone recognition . Gastrointest Endosc (1994) 40: 708-715

11.- Brambs, H..-J., H.-G. Leser, R.Salm, I. A. Shah et al : PerKutane transherpatische Cholangioskopie. Eine neue Methode zur Diagnostik von Malignomen der Galenwege.Disch.med. Wschr. (1987) 112: 1943-1496

12.- Nimura , Yg Staging of Biliary Carcinoma: Cholangiography and Cholangioscopy. Endoscopy (1993) 25:76-80

13.- Schmitt, W., H. Von Sanden , W. Wegerle, R.Ottenjann: Perorale und transhepatische Cholangioskopie . Leber Magen Darm (1991) 3: 116-124

14.- Kohler, B., M. Maier, J.F. Riemann: Endoskopie der Verdauungsorgane mit Biopsie und Zytologie. In E.G. Hahn, J. F. Riemann: Klinische Gastroenterologie (1996) 130-196

15.- Kozareck RA. Direct pancreatoscopy. Gastrointest Endosc Clin N Am (1995) 51: 259-67

16.- Becker, VgDer Wirsung’ sche Gang und die klinische Morphologie der Bauchspeicheldrüse. Internist (1989) 30:759-763

17.- Jung, M., A. Zipf, D. Schoonbroodt, G. Hermann, W.F. Caspary: Pankreatikoskopie zur differential diagnose von Pankreasgangstenosen. Endosk heute (1994) 3:231-236

18.- Foerster E. C., P. Störmer, M.U. Schneider, W. Mate, G. Domschke: Transpapillary miniscopy and mini-biopsy of the pancreatic duct. Endoscopy (1990) 22: 78-80

19.- Tajiri, H., M. Kobayashi, H. Niwa, S Furui: Clinical application of an ultra-thin pankreatoscope using a sequential video converter. Gastrointest Endosc. (1993) 39: 371-4

20.- Özkan, H., H. Saisho, T. Yamguchi, T. Tsuyuguchi, T. Ishihara. Y. Kikuchi, M. Ohto: Clinical usefulness of a new miniscope in the diagnosis of disease. Gastrointest Endosc. (1995) 42: 480-5

21.- Schoonbroodt D, A. Zipf, G. Hermann, H.Wenisch, M. Jung: Pancreatoscopy and diagnosis of mucinous neoplasms of the pancreas. Gastrointest Endosc (1996); 44: 479-82

22.- Jung, M., A. Zipf, D. Schoonbroodt,G. Hermann, W.F. Caspary: Is Pancreatoscopy of some benefit in clarifying the diagnosis of pancreatic duct lesions? (1998); 30: 273- 280

23.- Neuhaus, H., W. Hofmann, M. Classen : Laser lithotripsy of pancreatic and biliary stones via 3.4 mm nd 3,7 mm miniscopes: first clinical results. Endoscopy (1992) 24: 208-214

24.- Jakobs, R., H.Adamek, M Maier, C. Benz: Fluoroscopic-guided laserlithotripsy vs extracorporeal shock- wave lithotripsy for retained bile duct stones A prospective randomized study. Gastroenterology (1996) 110:458 (Abstract)

25.- Yasuda, K.: Ultrasonic probes for pancreaticobiliary strictures. Gastrointest Endosc 43: S35-S37

26.- Tamada, K., N. Kanai, N. Ueno, M. Ichiyama et al: Limitations of Intraductal Ultrasonography in Differentiating between Bile Duct Cancer in Stage T1 and Stage T2: In -vitro and In- vivo Studies. Endoscopy (1997) 29: 721-725

27.- Furukawa, T., K. Oohashi, K. Yamao, Y. Naitoh et al : Intraductal Ultrasonography of the Pancreas: Development and Clinical Potential .Endoscopy (1997)29: 561- 569.